This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The COBRE has 5 objectives: 1) Development of a strong mentoring group of established investigators with complimentary backgrounds in stem cell biology, molecular biology, neurobiology, and transcriptional regulation of differentiation, pulmonary physiology, and biology, and the translation of basic research to clinical therapy. 2) The enhancement of infrastructure support by providing core laboratories, administrative support, and total resources to increase the research competitiveness of our faculty. 3) Recruit and retain funded junior and established faculty so as to continue the establishment of RIH as a major stem cell research center. 4) Determine the true phenotype of marrow stem cells and its tissue fate to study the transfer of phenotype information via microvesicles from injured tissue, and to define mechanisms of transcriptional control and differentiation. 5) Translate basic stem cell studies into clinical trials on tissue restoration or correction in patients with chronic diseases and apply insights into approaches to cancer. An experienced mentoring group will support three full projects and two pilots led by junior investigators. The work is thematically coordinated around stem cell biology in general and approaches to modulating the stem cell phenotype. The current three projects are: 1) Injured lung and its influence on marrow cell phenotype, 2) Tyrosine phosphatase Shp2 in stem cell property maintenance, and 3) Determining the transcriptional regulation and cell signaling events that shape the molecular identity of Dopamine neuron progenitors and specify subtypes of midbrain Dopamine neurons. The pilot projects are: 1) the study of cycling hematopoietic stem cells, and 2) human induced pluripotent stem cell (iPSC) technology applied to brain disease. The scientific projects are supported by the administrative, flow cytometry, and molecular supports cores. There are ongoing plans for continued monitoring with the junior PIs presenting weekly to the mentors, and with a defined plan for progressive development of R01 grants by each of the individuals. New faculty are currently being recruited, and this COBRE clearly facilitates continued development of The Center for Stem Cell Biology. The grant holds great promise for expanding our understanding of stem cell biology in developing new approaches for tissue regeneration and cancer therapy.